Project description:This study was performed to investigate the effect of aging and high fat diet on gut microbiota in F344 rats by the pyrosequencing method.
Project description:Previous studies showed that aging in coronary arteries is associated with pro-inflammatory phenotypic changes and decreased NO bioavailability, which, we hypothesized, promotes vascular disease by inducing endothelial apoptosis. To test this hypothesis we characterized pro-apoptotic alterations in the phenotype of coronary arteries of aged (26 month old) and young (3 month old) F344 rats. DNA fragmentation analysis and TUNEL assay showed that in aged vessels there was a ~4 fold increase in the number of apoptotic endothelial cells. Analysis of the expression of apoptosis-related genes (microarray, real-time PCR) showed that in aged coronary arteries there was an increased expression of TNFa, TNFb, caspase 9 and an increased presence of cleaved caspase 3 and caspase 9 (Western blotting), whereas expression of TNFR1 and that of TRADD, Bcl-2, Bcl-X(L), Bid, Bax, caspase 8 and caspase 3 were unchanged. We propose that aging-induced up-regulation of TNFa and decreased bioavailability of NO promote endothelial apoptosis in coronary arteries that may lead to the development of endothelial dysfunction and ischemic heart disease in the elderly. Keywords: repeat sample
Project description:Previous studies showed that aging in coronary arteries is associated with pro-inflammatory phenotypic changes and decreased NO bioavailability, which, we hypothesized, promotes vascular disease by inducing endothelial apoptosis. To test this hypothesis we characterized pro-apoptotic alterations in the phenotype of coronary arteries of aged (26 month old) and young (3 month old) F344 rats. DNA fragmentation analysis and TUNEL assay showed that in aged vessels there was a ~4 fold increase in the number of apoptotic endothelial cells. Analysis of the expression of apoptosis-related genes (real-time PCR) showed that in aged coronary arteries there was an increased expression of TNFa, TNFb, caspase 9 and an increased presence of cleaved caspase 3 and caspase 9 (Western blotting), whereas expression of TNFR1 and that of TRADD, Bcl-2, Bcl-X(L), Bid, Bax, caspase 8 and caspase 3 were unchanged. Vascular expression and activity of TNFa convertase enzyme were preserved in aging. We propose that aging-induced up-regulation of TNFa and decreased bioavailability of NO promote endothelial apoptosis in coronary arteries that may lead to the development of endothelial dysfunction and ischemic heart disease in the elderly.
Project description:Previous studies showed that aging in coronary arteries is associated with pro-inflammatory phenotypic changes and decreased NO bioavailability, which, we hypothesized, promotes vascular disease by inducing endothelial apoptosis. To test this hypothesis we characterized pro-apoptotic alterations in the phenotype of coronary arteries of aged (26 month old) and young (3 month old) F344 rats. DNA fragmentation analysis and TUNEL assay showed that in aged vessels there was a ~4 fold increase in the number of apoptotic endothelial cells. Analysis of the expression of apoptosis-related genes (real-time PCR) showed that in aged coronary arteries there was an increased expression of TNFa, TNFb, caspase 9 and an increased presence of cleaved caspase 3 and caspase 9 (Western blotting), whereas expression of TNFR1 and that of TRADD, Bcl-2, Bcl-X(L), Bid, Bax, caspase 8 and caspase 3 were unchanged. Vascular expression and activity of TNFa convertase enzyme were preserved in aging. We propose that aging-induced up-regulation of TNFa and decreased bioavailability of NO promote endothelial apoptosis in coronary arteries that may lead to the development of endothelial dysfunction and ischemic heart disease in the elderly. Keywords: other
Project description:Progressive aging is associated with changes in sympathetic nervous system (SNS) regulation, suggesting an effect of advancing age on the functionality of central sympathetic premotor neurons. The rostral ventral lateral medulla (RVLM) contains sympathetic premotor neurons and plays a key role in SNS regulation, and it is plausible to speculate that age-related changes in the molecular mechanisms in the RVLM may contribute to alterations in SNS regulation. The present study tested the hypothesis that aging is associated with altered gene expression in the RVLM with emphasis on immune system associated gene transcripts. RVLM tissue punches from young, middle-aged, and aged F344 rats were analyzed using Agilent’s whole rat genome microarray. The RVLM gene expression profile varied with age and an association between chronological age and specific RVLM gene expression patterns was observed (p<0.05, FDR<0.3). Functional analysis of RVLM microarray data via gene ontology profiling and pathway analysis has identified up-regulation of genes associated with immune- and stress- related responses, and down-regulation of genes associated with lipid biosynthesis and neurotransmission in aged compared with middle-aged and young rats. Differentially expressed genes associated with complement system and microglial cells were further validated by quantitative PCR with separate RVLM samples (p<0.05, FDR<0.1). The present results are the first to demonstrate age-related changes in the RVLM molecular mechanisms, modifications that may provide the molecular backdrop for understanding immune-associated changes in SNS regulation.
Project description:In order to gain insight into the effects of aging on susceptibility to environmental toxins, we characterized the expression of xenobiotic metabolizing enzymes (XMEs) from the livers of male Brown Norway and F344 rats across the adult lifespan. To examine metabolic processes across lifespan after challenge with a xenobiotic compound, Brown Norway rats were exposed to 1.0 g/kg body weight toluene by oral gavage in corn oil (4ml/kg body weight) or corn oil alone. Keywords: age effect on toxin susceptibility
Project description:It is known that short-term high fat diet consumption leads to significant memory impairments and an exaggerated proinflammatory phenotype in the aged rat brain. To gain a better understanding of the underlying mechanisms driving this cognitive and proinflammatory response, we conducted bulk RNAseq analysis of the hippocampus and amygdala from young adult and aged male rats.
Project description:Previous studies showed that aging in coronary arteries is associated with pro-inflammatory phenotypic changes and decreased NO bioavailability, which, we hypothesized, promotes vascular disease by inducing endothelial apoptosis. To test this hypothesis we characterized pro-apoptotic alterations in the phenotype of coronary arteries of aged (26 month old) and young (3 month old) F344 rats. DNA fragmentation analysis and TUNEL assay showed that in aged vessels there was a ~4 fold increase in the number of apoptotic endothelial cells. Analysis of the expression of apoptosis-related genes (real-time PCR) showed that in aged coronary arteries there was an increased expression of TNFa, TNFb, caspase 9 and an increased presence of cleaved caspase 3 and caspase 9 (Western blotting), whereas expression of TNFR1 and that of TRADD, Bcl-2, Bcl-X(L), Bid, Bax, caspase 8 and caspase 3 were unchanged. Vascular expression and activity of TNFa convertase enzyme were preserved in aging. We propose that aging-induced up-regulation of TNFa and decreased bioavailability of NO promote endothelial apoptosis in coronary arteries that may lead to the development of endothelial dysfunction and ischemic heart disease in the elderly. Keywords: repeat sample
Project description:To compare the transcriptional profile in aged and high fat diet-fed kidneys lacking tubular Cpt1a with floxed littermate controls.